Interferon Beta May Not Halt MS Progression

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The interferon beta drugs widely used in relapsing-remitting multiple sclerosis (MS) may not delay progression of the disease in real-world practice, researchers have found.

Note that the study results call into question the assumption of long-term benefit, which remains unproven.

The interferon beta drugs widely used in relapsing-remitting multiple sclerosis (MS) may not delay progression of the disease in real-world practice, researchers found.

In a prospective registry, the drugs didn't predict a lower risk of becoming disabled compared with untreated contemporary controls, instead yielding a hazard ratio of 1.30 after adjustment for disease duration and other baseline factors (P=0.14).

The numbers looked a little better for interferon beta users when compared with untreated historical controls from the pre-interferon era, but they still didn't reach significance (adjusted HR 0.77, P=0.07), Helen Tremlett, PhD, of the University of British Columbia in Vancouver, and colleagues reported in the July 18 issue of the Journal of the American Medical Association.

"The study is useful in terms of giving patients realistic expectations on what they can hope to gain in terms of benefits from the drug treatments," Tremlett said in a video interview with the journal.

However, clinicians and patients shouldn't abandon interferon beta over these results, Tobias Derfuss, MD, and Ludwig Kappos, MD, both of the University Hospital Basel, Switzerland, cautioned in an accompanying editorial.

Controlled clinical trials have shown that interferon beta and other disease-modifying drugs cut down on relapse frequency and related progression of impairment and disability in MS.

"The common but disputed assumption has been that these clinical and radiographic findings in studies limited to 2 to 3 years' duration translate into long-term benefits, with delay or prevention of long-term disability in patients typically seen in a neurological practice," the editorial explained, which is key for a disease with an average duration of 30-plus years.

But drug efficacy often isn't as good in real-world settings with broader patient populations and much longer durations of treatment without the highly structured, supportive follow-up used in trials, Tremlett's group noted.

The bottom line is that the results call into question the assumption of long-term benefit, which remains unproven, the researchers and editorialists agreed.

Until more effective treatment options can be developed, identifying subgroups of patients who benefit more from interferon beta is needed, both groups concurred.

The study included all 2,656 adults with definite relapsing-remitting MS who reached broad eligibility criteria for interferon beta treatment from 1985 to 2004 in a database covering the four MS clinics in British Columbia, estimated to capture 80% of the MS population in the province.

Still, though, it may have been underpowered.

The 40% risk reduction assumed in the power calculation with interferon beta was more than the 30% found in the pivotal studies in relapsing-remitting MS, Derfuss and Kappos pointed out.

Another concern was bias. The contemporary controls untreated with interferon beta likely included many who didn't qualify for treatment because their disease was relatively benign, the editorialists suggested.

That was supported by the differing direction of the hazard ratio for progression compared with the historical pre-1995 controls, a group expected to have less indication bias, and by differences in baseline characteristics, they wrote.

The untreated patients in the contemporary 1995-2004 group had lower scores on the Expanded Disability Status Scale (EDSS), lower annualized relapse rates during the 2 years prior to inclusion in the analysis, and longer times from first symptoms to baseline.

A propensity score-adjusted analysis turned up similar results, though, for the main outcome measure of time from interferon beta treatment eligibility to confirmed and sustained disability marked by a score of 6 on the 10-point EDSS, reflecting loss of the ability to walk 100 m (109 yards) without a cane or other help.

Adjustment for comorbidities and socioeconomic status in addition to the potential confounders of sex, age, disease duration, and EDSS score at baseline likewise didn't change the findings.

Other limitations included consideration of all interferon beta drugs together and lack of data on neutralizing antibodies that may be associated with reduced effectiveness of the drugs.

The study was supported by grants from the Canadian Institutes of Health Research and the National Multiple Sclerosis Society. The British Columbia Multiple Sclerosis database has been funded from those sources and also by an unrestricted grant from Donald Paty, MD, of the University of British Columbia, and the MS/MRI Research Group.

Tremlett reported being funded by the Multiple Sclerosis Society of Canada, being a Michael Smith Foundation for Health Research Scholar, and being the Canada Research Chair for Neuroepidemiology and Multiple Sclerosis. She also has received research support from the NMSS, CIHR, and UK Multiple Sclerosis Trust.

Kappos and Derfuss reported that their institution receives drug company grants and/or payments for various activities including development of educational presentations, service on speakers bureaus, board memberships, and consultancies.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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